Five Years of GWAS Discovery

McClellan, 2010, Genetic heterogeneity in human disease, Cell, 141, 210, 10.1016/j.cell.2010.03.032

Crow, 2011, ‘The missing genes: what happened to the heritability of psychiatric disorders?’, Mol. Psychiatry, 16, 362, 10.1038/mp.2010.92

Manolio, 2009, Finding the missing heritability of complex diseases, Nature, 461, 747, 10.1038/nature08494

Botstein, 2003, Discovering genotypes underlying human phenotypes: Past successes for mendelian disease, future approaches for complex disease, Nat. Genet., 33, 228, 10.1038/ng1090

Hartl, 1997

Hill, 1968, The effects of inbreeding at loci with heterozygote advantage, Genetics, 60, 615, 10.1093/genetics/60.3.615

Altshuler, 2005, A haplotype map of the human genome, Nature, 437, 1299, 10.1038/nature04226

Dewan, 2006, HTRA1 promoter polymorphism in wet age-related macular degeneration, Science, 314, 989, 10.1126/science.1133807

Klein, 2005, Complement factor H polymorphism in age-related macular degeneration, Science, 308, 385, 10.1126/science.1109557

2007, Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls, Nature, 447, 661, 10.1038/nature05911

Franke, 2010, Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci, Nat. Genet., 42, 1118, 10.1038/ng.717

Anderson, 2011, Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47, Nat. Genet., 43, 246, 10.1038/ng.764

Lango Allen, 2010, Hundreds of variants clustered in genomic loci and biological pathways affect human height, Nature, 467, 832, 10.1038/nature09410

Yang, 2011, Genome partitioning of genetic variation for complex traits using common SNPs, Nat. Genet., 43, 519, 10.1038/ng.823

Yang, 2010, Common SNPs explain a large proportion of the heritability for human height, Nat. Genet., 42, 565, 10.1038/ng.608

Eyre-Walker, 2010, Evolution in health and medicine Sackler colloquium: Genetic architecture of complex traits and its implications for fitness and genome-wide association studies, Proc. Natl. Acad. Sci. USA, 107, 1752, 10.1073/pnas.0906182107

Pritchard, 2001, Are rare variants responsible for susceptibility to complex diseases?, Am. J. Hum. Genet., 69, 124, 10.1086/321272

Khor, 2011, Genetics and pathogenesis of inflammatory bowel disease, Nature, 474, 307, 10.1038/nature10209

Danoy, 2010, Association of variants at 1q32 and STAT3 with ankylosing spondylitis suggests genetic overlap with Crohn's disease, PLoS Genet., 6, e1001195, 10.1371/journal.pgen.1001195

Cotsapas, 2011, Pervasive sharing of genetic effects in autoimmune disease, PLoS Genet., 7, e1002254, 10.1371/journal.pgen.1002254

McCarthy, 2010, Genomics, type 2 diabetes, and obesity, N. Engl. J. Med., 363, 2339, 10.1056/NEJMra0906948

Kooner, 2011, Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci, Nat. Genet., 43, 984, 10.1038/ng.921

Yamauchi, 2010, A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B, Nat. Genet., 42, 864, 10.1038/ng.660

Shu, 2010, Identification of new genetic risk variants for type 2 diabetes, PLoS Genet., 6, e1001127, 10.1371/journal.pgen.1001127

Yasuda, 2008, Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus, Nat. Genet., 40, 1092, 10.1038/ng.207

Unoki, 2008, SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations, Nat. Genet., 40, 1098, 10.1038/ng.208

Tsai, 2010, A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese, PLoS Genet., 6, e1000847, 10.1371/journal.pgen.1000847

Below, 2011, Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals, Diabetologia, 54, 2047, 10.1007/s00125-011-2188-3

Parra, 2011, Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas, Diabetologia, 54, 2038, 10.1007/s00125-011-2172-y

Grant, 2006, Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes, Nat. Genet., 38, 320, 10.1038/ng1732

Prokopenko, 2009, Variants in MTNR1B influence fasting glucose levels, Nat. Genet., 41, 77, 10.1038/ng.290

Dupuis, 2010, New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk, Nat. Genet., 42, 105, 10.1038/ng.520

Saxena, 2010, Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge, Nat. Genet., 42, 142, 10.1038/ng.521

Weedon, 2006, A common haplotype of the glucokinase gene alters fasting glucose and birth weight: Association in six studies and population-genetics analyses, Am. J. Hum. Genet., 79, 991, 10.1086/509517

Larsen, 2005, Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity, J. Clin. Endocrinol. Metab., 90, 219, 10.1210/jc.2004-0497

Speliotes, 2010, Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index, Nat. Genet., 42, 937, 10.1038/ng.686

Frayling, 2007, A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity, Science, 316, 889, 10.1126/science.1141634

Meyre, 2009, Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations, Nat. Genet., 41, 157, 10.1038/ng.301

Scherag, 2010, Two new Loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and german study groups, PLoS Genet., 6, e1000916, 10.1371/journal.pgen.1000916

Willer, 2009, Six new loci associated with body mass index highlight a neuronal influence on body weight regulation, Nat. Genet., 41, 25, 10.1038/ng.287

Walters, 2010, A new highly penetrant form of obesity due to deletions on chromosome 16p11.2, Nature, 463, 671, 10.1038/nature08727

Heard-Costa, 2009, NRXN3 is a novel locus for waist circumference: A genome-wide association study from the CHARGE Consortium, PLoS Genet., 5, e1000539, 10.1371/journal.pgen.1000539

Heid, 2010, Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution, Nat. Genet., 42, 949, 10.1038/ng.685

Kilpelainen, 2011, Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile, Nat. Genet., 43, 753, 10.1038/ng.866

Sawcer, 2011, Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis, Nature, 476, 214, 10.1038/nature10251

Burton, 2007, Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants, Nat. Genet., 39, 1329, 10.1038/ng.2007.17

Evans, 2011, Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility, Nat. Genet., 43, 761, 10.1038/ng.873

Suzuki, 2003, Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis, Nat. Genet., 34, 395, 10.1038/ng1206

Padyukov, 2004, A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis, Arthritis Rheum., 50, 3085, 10.1002/art.20553

Voight, 2010, Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis, Nat. Genet., 42, 579, 10.1038/ng.609

Small, 2011, Identification of an imprinted master trans regulator at the KLF14 locus related to multiple metabolic phenotypes, Nat. Genet., 43, 561, 10.1038/ng1011-1040c

Freathy, 2010, Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight, Nat. Genet., 42, 430, 10.1038/ng.567

Gerken, 2007, The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase, Science, 318, 1469, 10.1126/science.1151710

Church, 2009, A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene, PLoS Genet., 5, e1000599, 10.1371/journal.pgen.1000599

Church, 2010, Overexpression of Fto leads to increased food intake and results in obesity, Nat. Genet., 42, 1086, 10.1038/ng.713

Freathy, 2008, Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI, Diabetes, 57, 1419, 10.2337/db07-1466

Teslovich, 2010, Biological, clinical and population relevance of 95 loci for blood lipids, Nature, 466, 707, 10.1038/nature09270

Gieger, 2011, New gene functions in megakaryopoiesis and platelet formation, Nature, 480, 201, 10.1038/nature10659

Mihaescu, 2011, Genetic risk profiling for prediction of type 2 diabetes, PLoS Curr., 3, RRN1208, 10.1371/currents.RRN1208

Elliott, 2009, Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease, JAMA, 302, 37, 10.1001/jama.2009.954

Owen, 2010, Assessment of high-sensitivity C-reactive protein levels as diagnostic discriminator of maturity-onset diabetes of the young due to HNF1A mutations, Diabetes Care, 33, 1919, 10.2337/dc10-0288

Thanabalasingham, 2011, A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes, Diabetologia, 54, 2801, 10.1007/s00125-011-2261-y

Zhou, 2011, Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes, Nat. Genet., 43, 117, 10.1038/ng.735

Stefansson, 2005, A common inversion under selection in Europeans, Nat. Genet., 37, 129, 10.1038/ng1508

Kong, 2004, Recombination rate and reproductive success in humans, Nat. Genet., 36, 1203, 10.1038/ng1445

Hinch, 2011, The landscape of recombination in African Americans, Nature, 476, 170, 10.1038/nature10336

Seldin, 2007, Argentine population genetic structure: Large variance in Amerindian contribution, Am. J. Phys. Anthropol., 132, 455, 10.1002/ajpa.20534

Seldin, 2006, European population substructure: Clustering of northern and southern populations, PLoS Genet., 2, e143, 10.1371/journal.pgen.0020143

Tian, 2006, A genomewide single-nucleotide-polymorphism panel with high ancestry information for African American admixture mapping, Am. J. Hum. Genet., 79, 640, 10.1086/507954

McEvoy, 2009, Geographical structure and differential natural selection among North European populations, Genome Res., 19, 804, 10.1101/gr.083394.108

Heath, 2008, Investigation of the fine structure of European populations with applications to disease association studies, Eur. J. Hum. Genet., 16, 1413, 10.1038/ejhg.2008.210

Novembre, 2008, Genes mirror geography within Europe, Nature, 456, 98, 10.1038/nature07331

Price, 2008, Discerning the ancestry of European Americans in genetic association studies, PLoS Genet., 4, e236, 10.1371/journal.pgen.0030236

Manolio, 2010, Genomewide association studies and assessment of the risk of disease, N. Engl. J. Med., 363, 166, 10.1056/NEJMra0905980

Sivakumaran, 2011, Abundant pleiotropy in human complex diseases and traits, Am. J. Hum. Genet., 89, 607, 10.1016/j.ajhg.2011.10.004

Dickson, 2010, Rare variants create synthetic genome-wide associations, PLoS Biol., 8, e1000294, 10.1371/journal.pbio.1000294

Anderson, 2011, Synthetic associations are unlikely to account for many common disease genome-wide association signals, PLoS Biol., 9, e1000580, 10.1371/journal.pbio.1000580

Wray, 2011, Synthetic associations created by rare variants do not explain most GWAS results, PLoS Biol., 9, e1000579, 10.1371/journal.pbio.1000579

Visscher, 2011, Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses, Molecular Psychiatry

Hunter, 2007, Drinking from the fire hose—Statistical issues in genomewide association studies, N. Engl. J. Med., 357, 436, 10.1056/NEJMp078120

Pryce, 2011, Polymorphic regions affecting human height also control stature in cattle, Genetics, 187, 981, 10.1534/genetics.110.123943

Bodmer, 1986, Human genetics: The molecular challenge, Cold Spring Harb. Symp. Quant. Biol., 51, 1, 10.1101/SQB.1986.051.01.003

Risch, 1996, The future of genetic studies of complex human diseases, Science, 273, 1516, 10.1126/science.273.5281.1516

Wray, 2005, Allele frequencies and the r2 measure of linkage disequilibrium: impact on design and interpretation of association studies, Twin Res. Hum. Genet., 8, 87, 10.1375/twin.8.2.87

McClellan, 2007, Schizophrenia: A common disease caused by multiple rare alleles, Br. J. Psychiatry, 190, 194, 10.1192/bjp.bp.106.025585

Craddock, 2007, Phenotypic and genetic complexity of psychosis. Invited commentary on … Schizophrenia: a common disease caused by multiple rare alleles, Br. J. Psychiatry, 190, 200, 10.1192/bjp.bp.106.033761

Lander, 1996, The new genomics: Global views of biology, Science, 274, 536, 10.1126/science.274.5287.536

Chakravarti, 1999, Population genetics—Making sense out of sequence, Nat. Genet., 21, 56, 10.1038/4482

Reich, 2001, On the allelic spectrum of human disease, Trends Genet., 17, 502, 10.1016/S0168-9525(01)02410-6

Risch, 1990, Linkage strategies for genetically complex traits. I. Multilocus models, Am. J. Hum. Genet., 46, 222

Slatkin, 2008, Exchangeable models of complex inherited diseases, Genetics, 179, 2253, 10.1534/genetics.107.077719

Hill, 2008, Data and theory point to mainly additive genetic variance for complex traits, PLoS Genet., 4, e1000008, 10.1371/journal.pgen.1000008

Wang, 2010, Interpretation of association signals and identification of causal variants from genome-wide association studies, Am. J. Hum. Genet., 86, 730, 10.1016/j.ajhg.2010.04.003

Nejentsev, 2009, Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes, Science, 324, 387, 10.1126/science.1167728

Momozawa, 2011, Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease, Nat. Genet., 43, 43, 10.1038/ng.733

Rivas, 2011, Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease, Nat. Genet., 43, 1066, 10.1038/ng.952

Wang, 2010, Strategies for genetic studies of complex diseases, Cell, 142, 351, 10.1016/j.cell.2010.07.025

Hyttinen, 2003, Genetic liability of type 1 diabetes and the onset age among 22,650 young Finnish twin pairs: A nationwide follow-up study, Diabetes, 52, 1052, 10.2337/diabetes.52.4.1052

Polychronakos, 2011, Understanding type 1 diabetes through genetics: Advances and prospects, Nat. Rev. Genet., 12, 781, 10.1038/nrg3069

Poulsen, 1999, Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance—A population-based twin study, Diabetologia, 42, 139, 10.1007/s001250051131

Magnusson, 2002, Familial resemblance of body mass index and familial risk of high and low body mass index. A study of young men in Sweden, Int. J. Obes. Relat. Metab. Disord., 26, 1225, 10.1038/sj.ijo.0802041

Schousboe, 2003, Sex differences in heritability of BMI: A comparative study of results from twin studies in eight countries, Twin Res., 6, 409, 10.1375/136905203770326411

Tysk, 1988, Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking, Gut, 29, 990, 10.1136/gut.29.7.990

Hawkes, 2009, Twin studies and the heritability of MS: A conclusion, Mult. Scler., 15, 661, 10.1177/1352458509104592

Brown, 1997, Susceptibility to ankylosing spondylitis in twins: The role of genes, HLA, and the environment, Arthritis Rheum., 40, 1823, 10.1002/art.1780401015

Brown, 2011, Progress in the genetics of ankylosing spondylitis, Brief. Funct. Genomics, 10, 249, 10.1093/bfgp/elr023

MacGregor, 2000, Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins, Arthritis Rheum., 43, 30, 10.1002/1529-0131(200001)43:1<30::AID-ANR5>3.0.CO;2-B

Lichtenstein, 2009, Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: A population-based study, Lancet, 373, 234, 10.1016/S0140-6736(09)60072-6

Purcell, 2009, Common polygenic variation contributes to risk of schizophrenia and bipolar disorder, Nature, 460, 748, 10.1038/nature08185

Lichtenstein, 2000, Environmental and heritable factors in the causation of cancer—Analyses of cohorts of twins from Sweden, Denmark, and Finland, N. Engl. J. Med., 343, 78, 10.1056/NEJM200007133430201

Turnbull, 2010, Genome-wide association study identifies five new breast cancer susceptibility loci, Nat. Genet., 42, 504, 10.1038/ng.586

Orstavik, 1985, Factor VIII and factor IX in a twin population. Evidence for a major effect of ABO locus on factor VIII level, Am. J. Hum. Genet., 37, 89

de Lange, 2001, The genetics of haemostasis: A twin study, Lancet, 357, 101, 10.1016/S0140-6736(00)03541-8

Smith, 2010, Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium, Circulation, 121, 1382, 10.1161/CIRCULATIONAHA.109.869156

Visscher, 2006, Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings, PLoS Genet., 2, e41, 10.1371/journal.pgen.0020041

Silventoinen, 2003, Heritability of adult body height: A comparative study of twin cohorts in eight countries, Twin Res., 6, 399, 10.1375/136905203770326402

Peacock, 2002, Genetics of osteoporosis, Endocr. Rev., 23, 303, 10.1210/edrv.23.3.0464

Duncan, 2011, Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk, PLoS Genet., 7, e1001372, 10.1371/journal.pgen.1001372

Dalageorgou, 2008, Heritability of QT interval: how much is explained by genes for resting heart rate?, J. Cardiovasc. Electrophysiol., 19, 386, 10.1111/j.1540-8167.2007.01030.x

Russell, 1998, Heritability of ECG measurements in adult male twins, J. Electrocardiol., 30, 64, 10.1016/S0022-0736(98)80034-4

Shah, 2009, Genetics of cardiac repolarization, Nat. Genet., 41, 388, 10.1038/ng0409-388

Hunt, 1989, Genetic heritability and common environmental components of resting and stressed blood pressures, lipids, and body mass index in Utah pedigrees and twins, Am. J. Epidemiol., 129, 625, 10.1093/oxfordjournals.aje.a115175

Evans, 1999, Genetic and environmental causes of variation in basal levels of blood cells, Twin Research: The Official Journal of the International Society for Twin Studies, 2, 250, 10.1375/twin.2.4.250